A Study of ARRY-438162 (MEK162) in Patients With Advanced Cancer

This study has been completed.

Sponsor:

Array BioPharma

ClinicalTrials.gov Identifier:

NCT00959127

First Posted: August 14, 2009

Last Update Posted: February 13, 2013

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government.
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Establish the maximum tolerated dose (MTD) of the study drug. [ Time Frame: Part 1, one year ]

Characterize the safety profile of the study drug in terms of adverse events, clinical laboratory tests and electrocardiograms. [ Time Frame: Parts 1, 2 and 3: two years ]

Characterize the pharmacokinetics (PK) of the study drug and metabolite. [ Time Frame: Parts 1, 2 and 3: two years ]

Original Primary Outcome Measures ICMJE (submitted: August 13, 2009)

Characterize the safety profile of study drug [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Determine the maximum tolerated dose (MTD) of study drug through review of all available Cycle 1 data and assessment of dose limiting toxicities (DLTs) [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Characterize the plasma PK of study drug and a metabolite [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Assess the efficacy of the study drug in terms of tumor response, duration of response, duration of stable disease, progression-free survival and overall survival. [ Time Frame: Parts 1, 2 and 3: two years ]

Assess possible PK/pharmacodynamic (PD) or PK/efficacy and safety correlations. [ Time Frame: Parts 1, 2 and 3: two years ]

Obtain preliminary estimates of efficacy of study drug [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Assess body weight changes as a measure of clinical benefit of study drug [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Assess PD effects of study drug in pre- and post-dose serum, skin and hair follicle samples as feasible [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Assess mRNA and protein expression levels and mutation status in archival or fresh predose tumor tissue as feasible [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Assess possible PK/PD or PK/efficacy and safety correlations [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Characterize the metabolite profile of study drug in plasma [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Assess lean body mass changes as a potential measure of clinical benefit of study drug [ Time Frame: 1 year, all patients will remain on study until progression of disease, unacceptable toxicity, or another discontinuation criterion is met ]

Current Other Outcome Measures ICMJE

Not Provided

Original Other Outcome Measures ICMJE

Not Provided

Descriptive Information

Brief Title ICMJE

A Study of ARRY-438162 (MEK162) in Patients With Advanced Cancer

Official Title ICMJE

Not Provided

Brief Summary

This is a Phase 1 study during which patients with advanced solid tumors will receive investigational study drug ARRY-438162 (MEK162).

This study has 3 parts. In the first part, patients with advanced solid tumors will receive increasing doses of study drug in order to achieve the highest dose of the study drug possible that will not cause unacceptable side effects. Approximately 30 patients from the US will be enrolled in Part 1. (Active, not recruiting)

In the second part of the study, patients with advanced or metastatic biliary cancer will receive the best dose of study drug determined from the first part of the study and will be followed to see what side effects and effectiveness the study drug has, if any, in treating the cancer. Approximately 25 patients from the US will be enrolled in Part 2. (Active, not recruiting)

In the third part of the study, patients with metastatic colorectal cancer (CRC) will receive the best dose of the study drug determined from the first part of the study and will be followed to see what side effects and effectiveness the study drug has, if any, in treating the cancer. Approximately 25 patients with KRAS mutation (Active, not recruiting) and 15 patients with BRAF mutation (Active, not recruiting) from the US will be enrolled in Part 3.

Uncontrolled or symptomatic brain metastases (if the patient has brain metastases and is on steroids, the steroid dose must have been stable for at least 30 days).

History of central serous retinopathy, retinopathy visible at baseline that would be considered a risk factor for central serous retinopathy or retinal vein occlusion.

Concomitant malignancies or previous malignancies with less than a 2-year disease free interval at the time of enrollment; patients with adequately resected basal or squamous cell carcinoma of the skin, carcinoma in situ of the cervix, or stage A low grade prostate cancer may enroll irrespective of the time of diagnosis.

Prior treatment with a MEK inhibitor.

Treatment with prior chemotherapy, anticancer immunotherapy, monoclonal antibodies or other protein or peptide therapeutics within 21 days of the first dose of study drug.

Treatment with a small molecule targeted agent or anticancer hormonal therapy within 14 days of the first dose of study drug.

Treatment with prior radiotherapy within 28 days of initiating study drug (if the radiation portal covered ≤ 10% of the bone marrow reserve, the patient may be enrolled irrespective of the end date of radiotherapy).

Major surgery within 4 weeks or minor surgery within 7 days prior to the first dose of study drug.